Suppression of EEG Epileptiform Discharges by Acetazolamide in MeCP2-Deficient Mice
Abstract number :
1.289
Submission category :
7. Antiepileptic Drugs
Year :
2011
Submission ID :
14702
Source :
www.aesnet.org
Presentation date :
12/2/2011 12:00:00 AM
Published date :
Oct 4, 2011, 07:57 AM
Authors :
S. Aljarallah, C. Wu, K. Shampur, J. Eubanks, L. Zhang
Rationale: Rett s syndrome is an X-linked neurodevelopmental disorder which causes severe impairment of motor and verbal communication skills. Seizures were described in a large percentage of patients with this disorder. MeCP2 gene mutations are found in the vast majority of cases. Using MeCP2-deficent mice as a model, we explored the effects of different anticonvulsants on EEG discharge of these mice. Methods: MeCP2-dificent male and female mice were obtained from Jackson Lab. Surgical implantation of intracranial EEG electrodes was done at ages of 4-8 weeks (male), 2-3 moths (young females) and 8-9 months (adult females). Baseline EEG recordings were conducted 2 weeks post surgery and then repeatedly following acetazolamide injections. During EEG recordings, the animals stayed in home cages and moved freely. Young adult (3 months) wild type mice underwent similar electrode implantation and EEG monitoring. A clinically available injection form of acetazolamide was used to treat MeCP2-deficient mice (40mg/Kg, intra-peritoneal injections, daily for 7 days).Works are in progress to quantify the effects of acetazolamide and to treat these young and adult female mice with valproic acid at different doses. We plan to conduct similar acetazolamide treatments in other 10 MeCP2-deficient female mice. In addition, we will examine the effects of combined administration of acetazolamide and valproic acid in MeCP2-deficeint mice.Results: Repeated EEG recordings over a 3-month period revealed no epileptiform discharges EEG in wild type mice (n=6). In contrary, baseline EEG recordings revealed cortical discharges in all 7 MeCP2-deficient mice examined (2 male and 5 female mice). These discharges occurred largely during wake immobility and manifested with large-amplitude rhythmic spikes (6-8 spikes per sec). Also, epileptiform discharges were surprisingly seen in the young females group. One male mouse died after the baseline recordings. Thus, acetazolamide treatments were conducted in 1 male and 5 female MeCP2-dificent mice. The incidence and duration of these EEG discharges were greatly decreased when examined within 2 hours following a single acetazolamide injection. EEG discharges also appeared to be decreased relative to the baseline when examined 1 and 2 week after the last acetazolamide injection. However, the male mouse died 2 days after the last injection of acetazolamide.Conclusions: Our observations indicate that cortical EEG discharges are a neurophysiological fingerprint of MeCP2-difficent mice. These discharges were seen even in younger mice (2-3 months), which could represent an early manifestation of the disease. In addition, our present observations suggest that such discharges are sensitive to suppression by acetazolamide treatments. This work is supported by IRSF HeART grant 2735.
Antiepileptic Drugs